TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14737	44434;44435;44436	chr2:178630313;178630312;178630311	chr2:179495040;179495039;179495038
N2AB	13096	39511;39512;39513	chr2:178630313;178630312;178630311	chr2:179495040;179495039;179495038
N2A	12169	36730;36731;36732	chr2:178630313;178630312;178630311	chr2:179495040;179495039;179495038
N2B	5672	17239;17240;17241	chr2:178630313;178630312;178630311	chr2:179495040;179495039;179495038
Novex-1	5797	17614;17615;17616	chr2:178630313;178630312;178630311	chr2:179495040;179495039;179495038
Novex-2	5864	17815;17816;17817	chr2:178630313;178630312;178630311	chr2:179495040;179495039;179495038
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Ig-98
• Domain position: 63
• Structural Position: 145
• Q(SASA): 0.6259
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
R/C	rs748593243	-0.171	0.999	D	0.365	0.341	0.432493127443	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.66168E-04
R/C	rs748593243	-0.171	0.999	D	0.365	0.341	0.432493127443	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
R/C	rs748593243	-0.171	0.999	D	0.365	0.341	0.432493127443	gnomAD-4.0.0	6.20039E-06	None	None	None	None	N	None	1.3364E-05	3.337E-05	None	0	0	None	3.12735E-05	0	4.23945E-06	0	0
R/H	rs373298007	-1.211	0.071	N	0.187	0.119	None	gnomAD-2.1.1	1.39432E-04	None	None	None	None	N	None	3.72116E-04	6.23866E-04	None	0	5.18E-05	None	6.55E-05	None	4E-05	3.13E-05	0
R/H	rs373298007	-1.211	0.071	N	0.187	0.119	None	gnomAD-3.1.2	1.57924E-04	None	None	None	None	N	None	4.58915E-04	2.62433E-04	0	0	0	None	0	0	1.47E-05	0	0
R/H	rs373298007	-1.211	0.071	N	0.187	0.119	None	1000 genomes	3.99361E-04	None	None	None	None	N	None	8E-04	1.4E-03	None	None	0	0	None	None	None	0	None
R/H	rs373298007	-1.211	0.071	N	0.187	0.119	None	gnomAD-4.0.0	5.14578E-05	None	None	None	None	N	None	3.33538E-04	4.50375E-04	None	0	0	None	0	0	2.03492E-05	6.59181E-05	1.60159E-05
R/L	rs373298007	0.334	0.015	N	0.272	0.172	None	gnomAD-2.1.1	2.03785E-04	None	None	None	None	N	None	8.27E-05	0	None	0	2.69179E-03	None	3.27E-05	None	0	7.82E-06	1.40647E-04
R/L	rs373298007	0.334	0.015	N	0.272	0.172	None	gnomAD-3.1.2	1.31603E-04	None	None	None	None	N	None	4.83E-05	0	0	0	3.1068E-03	None	0	0	0	2.07297E-04	4.78469E-04
R/L	rs373298007	0.334	0.015	N	0.272	0.172	None	1000 genomes	5.99042E-04	None	None	None	None	N	None	0	0	None	None	3E-03	0	None	None	None	0	None
R/L	rs373298007	0.334	0.015	N	0.272	0.172	None	gnomAD-4.0.0	6.88171E-05	None	None	None	None	N	None	8.00491E-05	0	None	0	2.10347E-03	None	0	0	8.47883E-07	3.29591E-05	1.12111E-04

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
R/A	0.4445	ambiguous	0.4503	ambiguous	-0.204	Destabilizing	0.505	D	0.365	neutral	None	None	None	None	N
R/C	0.1335	likely_benign	0.1355	benign	0.014	Stabilizing	0.999	D	0.365	neutral	D	0.53196314	None	None	N
R/D	0.6629	likely_pathogenic	0.6901	pathogenic	0.093	Stabilizing	0.712	D	0.405	neutral	None	None	None	None	N
R/E	0.444	ambiguous	0.4372	ambiguous	0.199	Stabilizing	0.505	D	0.252	neutral	None	None	None	None	N
R/F	0.4347	ambiguous	0.4614	ambiguous	-0.13	Destabilizing	0.897	D	0.426	neutral	None	None	None	None	N
R/G	0.2681	likely_benign	0.2681	benign	-0.497	Destabilizing	0.826	D	0.402	neutral	N	0.418546185	None	None	N
R/H	0.0788	likely_benign	0.0794	benign	-1.054	Destabilizing	0.071	N	0.187	neutral	N	0.419742531	None	None	N
R/I	0.3046	likely_benign	0.3374	benign	0.565	Stabilizing	0.553	D	0.433	neutral	None	None	None	None	N
R/K	0.1098	likely_benign	0.1102	benign	-0.172	Destabilizing	0.014	N	0.156	neutral	None	None	None	None	N
R/L	0.2039	likely_benign	0.2119	benign	0.565	Stabilizing	0.015	N	0.272	neutral	N	0.465435133	None	None	N
R/M	0.3237	likely_benign	0.349	ambiguous	0.204	Stabilizing	0.897	D	0.395	neutral	None	None	None	None	N
R/N	0.4999	ambiguous	0.5282	ambiguous	0.347	Stabilizing	0.712	D	0.21	neutral	None	None	None	None	N
R/P	0.7929	likely_pathogenic	0.7931	pathogenic	0.331	Stabilizing	0.99	D	0.434	neutral	D	0.531768966	None	None	N
R/Q	0.0989	likely_benign	0.0984	benign	0.213	Stabilizing	0.712	D	0.317	neutral	None	None	None	None	N
R/S	0.432	ambiguous	0.445	ambiguous	-0.193	Destabilizing	0.826	D	0.33	neutral	N	0.425455715	None	None	N
R/T	0.2726	likely_benign	0.282	benign	0.081	Stabilizing	0.834	D	0.333	neutral	None	None	None	None	N
R/V	0.3741	ambiguous	0.4086	ambiguous	0.331	Stabilizing	0.553	D	0.384	neutral	None	None	None	None	N
R/W	0.1842	likely_benign	0.1798	benign	0.028	Stabilizing	0.995	D	0.385	neutral	None	None	None	None	N
R/Y	0.3234	likely_benign	0.3417	ambiguous	0.374	Stabilizing	0.897	D	0.441	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.